PROJECT SUMMARY - STEM CELLS, DIFFERENTIATION AND CANCER PROGRAM The Stem Cells, Differentiation and Cancer Program (SCDC), established at the time of the last CCSG renewal, brought together elements from two former AECC programs, Immuno-Oncology, and Cell Growth & Differentiation Control. This was catalyzed by the inception of the Institute for Stem Cell Research at Einstein and a newly formed Hemato-Oncology Division in the Department of Oncology. Since 2013, the program has evolved with the recruitment of new faculty members and increased breadth and depth in the hematological malignancies. At the same time, the program has strengthened its traditional role as a focal point for basic research with an emphasis on epigenetics/transcription and chromatin biology. The thematic aims of this program are to: (i) discover novel molecular and cellular mechanisms, that underlie regulation of normal and malignant stem cells, (ii) conduct basic studies to understand mechanisms of transcriptional regulation at the epigenetic and chromatin structure levels, and post-transcriptionally, and (iii) to decipher the molecular pathogenesis of hematological malignances and the development of therapies that target cancer-initiating stem cells, with translation into correlative studies and therapeutic initiatives. The latter are conducted, collaboratively, by members of the Experimental Therapeutics Program with expertise in the treatment of the hematological malignancies. The program has continued to make important discoveries and perform studies of fundamental transcriptional and epigenetic mechanisms controlling cell growth and differentiation. Members of this program have also made considerable progress in uncovering novel cell-intrinsic and -extrinsic mechanisms of regulation of normal and malignant stem cells, including pre-leukemic cell states. There have been important developments in the identification of new druggable targets leading to the development of novel drugs at AECC and in collaboration with pharma. The recruitment of new members has catalyzed the expansion of translational studies at the correlative and therapeutic levels, in collaboration with members of the Experimental Therapeutics Program. The program has also established a specialized facility to assess the effectiveness of a variety of drugs again leukemia-initiating stems cells that has relevance to studies on cancer-initiating progenitor cells in other AECC programs. There is robust research that addresses the characteristics of the hematological malignancies and their treatment, often at the molecular level, in the large minority population that makes up the AECC's Bronx catchment area. There are 31 program members from 11 departments. Current NCI funding is 2.4M (dc); total peer-reviewed funding is 10.3M (dc). There have been 480 publications since July 2013 of which 17% represent intra-programmatic, 19% inter-programmatic, and 57% represent collaborations with investigators at other institutions.